Download Influence of the Location of Left Anterior Descending

Influence of the Location of Left Anterior
Descending Coronary Artery Stenosis on Left
Ventricular Function During Exercise
KA-HEI LEONG, M.D.,
AND
ROBERT H. JONES, M.D.
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SUMMARY The purpose of this investigation was to determine if a stenosis of a coronary artery located
proximally caused greater deterioration of left ventricular function than a stenosis of a similar magnitude
located more distally in the artery. Twenty-six patients with isolated left anterior descending coronary artery
(LAD) lesions documented by cardiac catheterization were studied by radionuclide angiocardiography (RNA)
at rest and during exercise on a bicycle ergometer. Thirteen patients (nine males and four females) had a proximal lesion of the LAD averaging 91 ± 11% of the diameter of the lumen (group 1) and 13 patients (eight males
and five females) had a distal lesion averaging 88 12% of the lumen (group 2). The mean age of group 1 was
49 ± 9 years and the mean age of group 2 was 48 9 years. In group 1, the ejection fraction decreased from 63
± 8% to 55
i11% (p = 0.02), left ventricular end-diastolic volume (EDV) increased from 130 ± 32 ml to 174
± 34 ml (p = 0.001) and left ventricular end-systolic volume (ESV) increased from 49 ± 16 ml to 80 ± 26 ml
(p = 0.001) during exercise. In group 2, the ejection fraction and ESV showed no significant change during exercise. In this group, the left ventricular EDV increased from 117 ± 28 ml to 140 ± 37 ml (p = 0.04) during
exercise. The two groups showed no significant hemodynamic differences during the rest studies, but group 1
showed significantly lower ejection fraction and higher EDV and ESV during exercise. These findings indicate
that a stenotic lesion located at a more proximal level of the coronary arterial system reduces blood flow in a
larger area of myocardium, resulting in a more pronounced ischemic response to exercise than a similar lesion
located more distally.
mented by coronary arteriography to have significant
isolated LAD coronary artery stenosis were studied by
RNA at rest and during exercise. Each patient had a
baseline evaluation, including history, physical examination, ECG and chest radiograph, as well as
hematologic and chemical blood profiles. Patients
with episodic substernal chest tightness or pain accentuated by exercise or stress and partially or completely
relieved by rest were classified as having typical
angina pectoris. Patients with any uncharacteristic
aspect of the pain were classified as having atypical
angina. No patient had severe impairment of left ventricular function (resting ejection fraction less than
50%), cardiomyopathy, left ventricular aneurysm or
congestive heart failure.
Right and left cardiac catheterization and coronary
arteriography were performed in each patient. Coronary arteriograms were reviewed by three observers,
and the magnitude of atherosclerotic narrowing was
estimated as the percent of the diameter of the artery.
The magnitude of each stenotic lesion was categorized
as 0%, 25%, 50%, 75%, 95% or 100% of the vessel
diameter.4 The site of each stenosis was diagrammed
for later tabulation. For this study, all stenoses of 75%
or greater in major coronary arterial branches were
defined as hemodynamically significant, and stenoses
of less magnitude were considered to represent insignificant disease. This definition has been shown to
correlate with ultimate prognosis at this institution."
Thirteen patients showed a significant stenosis in the
LAD proximal to the first perforating branch, and
were designated group 1. Thirteen patients had significant stenosis in the LAD distal to the first septal
perforating branch, and were designated group 2.
The clinical characteristics of group 1 (table 1) were
quite similar to those of group 2 (table 2). Group 1 included nine males and four females, mean age 49
RADIONUCLIDE ANGIOCARDIOGRAPHY
(RNA) permits noninvasive measurement of left ventricular function in patients with coronary artery disease, and has been used to document impairment of
left ventricular function in patients with coronary
artery stenosis." 2 The magnitude of exercise-induced
left ventricular dysfunction has been related to the
anatomic extent of disease, and patients with stenosis
of more than one coronary artery showed more
deterioration of left ventricular function during exercise than patients with one-vessel coronary artery
stenosis.3 However, a moderate amount of individual
variation was observed among patients grouped by the
number of stenotic vessels. This individual variation
may have been the result of differences in severity of
stenosis or amount of collateral perfusion. In addition, stenotic lesions located more proximally in the
vessel might induce a greater functional impairment
than more distally located lesions.
The purpose of this investigation was to assess the
functional response in two groups of patients with
similar amounts of left anterior descending coronary
artery (LAD) stenosis to evaluate the influence of the
level of the stenosis on functional impairment during
exercise.
Methods
Twenty-six patients admitted to Duke University
Medical Center because of chest pain and docuFrom the Department of Surgery, Duke University Medical
Center, Durham, North Carolina.
Supported by grant HL-17670-05, SCOR, NIH.
Address for correspondence: Robert H. Jones, M.D., P.O. Box
2986, Duke University Medical Center, Durham, North Carolina
27710.
Received February 20, 1981; revision accepted April 27, 1981.
Circulation 65, No. 1, 1982.
109
CIRCULATION
110
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years, and group 2 included eight males and five
females, mean age 48 years. The mean body surface
area was 1.9 ± 0.2 in both groups. A prior myocardial
infarction was suggested by history or ECG in seven
patients of group 1 and five patients of group 2. No
patient had a documented myocardial infarction
within 6 months of the time of study. The number and
extent of significant stenoses were similar in groups 1
and 2 when expressed as the number with a 75%, 95%
or 100% stenosis. Moreover, the average of the significant stenosis was 91 ± 1 1% in group 1 and 88 ± 12%
in group 2. A similar number of stenoses considered
insignificant was present in both groups. Therefore,
the major difference between the two groups of
patients was the level of LAD stenosis.
Of the 13 patients with a stenosis in the proximal
LAD, seven had a stenosis located proximal to the
origin of the first anterolateral branch and six distal to
the first anterolateral branch but proximal to the first
septal perforating branch. Four of these patients had
stenoses extending more distally in the LAD, but the
stenosis was significant in only one patient. In the 13
patients in group 2, the significant stenosis was located
distal to the first septal perforating branch but proximal to the second anterolateral branch in each
patient. Three of these 13 patients also had insignificant stenoses in the proximal LAD. An insignificant
stenosis was observed in the circumflex or right coronary artery in eight patients in group I and seven patients in group 2.
Propranolol was discontinued at least 24 hours
before study in all patients who had received it. Rest
and exercise RNA were performed for each patient by
a previously described technique.6 The patient was
seated in an erect position on a bicycle ergometer
(Fitron, Lumex, Inc.) with a short, 21-gauge Teflon
catheter placed into an external jugular vein. The
heart rate was continuously monitored by telemetry of
a modified CM-5 lead, and blood pressure was
monitored at 1-minute intervals by a sphygmomanometer during rest, exercise and recovery.
The RNA was performed from an anterior projection using a Baird Atomic System Seventy-Seven multicrystal computerized gamma camera. Data were
acquired at 25-msec intervals for I minute after a
LAD STENOSIS PROXIMAl TO
FIRST SEPTAL PERFORATOR
VENTRICULAR
EJECTION
FRACT ION
(0/
)
70
bolus injection of 15 mCi of technetium-99m
pertechnetate.
After acquisition of a resting study, exercise was
begun at 200 kpm/min, and the work load was increased by 100-kpm/min increments each minute. A
second RNA was obtained during exercise when the
patient achieved an end point of chest pain suggestive
of angina, ECG ischemic changes or 85% of maximal
predicted heart rate for age.
Left ventricular ejection fraction (LVEF), enddiastolic volume (EDV) and end-systolic volume
(ESV) were calculated by data processing techniques
that have been assessed for accuracy and reproducibility.7 Wall motion was subjectively assessed using
static and dynamic images of the left ventricle
throughout the cardiac cycle.
The difference in individual rest and exercise measurements in each group were compared with a paired
t test. The hemodynamic measurements between
groups were compared by unpaired t tests. A p value
less than 0.05 was considered significant.
Results
The exercise end points achieved were similar in the
two patient groups. In the group 1 patients, with proximal LAD stenoses, heart rate increased from 74 ± 14
beats/min to 124 ± 27 beats/min and mean blood
pressure increased from 94 ± 11 mm Hg to 108 ± 15
mm Hg during exercise. Four patients achieved their
target heart rate and nine developed chest pain or STsegment depression during exercise. In the group 2
patients, with distal LAD stenoses, heart rate increased from 80 ± 15 beats/min to 138 ± 21
beats/min and mean blood pressure from 96 i 15 mm
Hg to 113 ± 22 mm Hg during exercise. Six patients
achieved their target heart rate and seven developed
chest pain or ST-segment depression during exercise.
In group 1 patients, LVEF decreased during exercise, from 63 ± 8% to 55 ± 11% (p = 0.02). In group
2, LVEF changed insignificantly, from 66 ± 8% to 65
± 10% during exercise (fig. 1). Although some individual variation was apparent in group 1, only two
subjects had a small increase in LVEF, and a marked
decrease was the predominant change. In some
patients in group 2, LVEF decreased during exercise,
LAD STENOSIS DISTAL TO
FIRST SEPTAL PERFORATOR
80
80
LEFT
VOL 65, No 1, JANUARY 1982
T
703
60
60 -
50
50
40
40o
REST
EXERCISE
I.
.X
II
P-NS
REST
EXERCISE
FIGURE 1. The 13 patients with a left
anterior descending coronary artery (LAD)
stenosis proximal to the first septal perforator show a marked decrease of left ventricular ejection fraction (L VEF) during exercise. Thirteen patients with a distal
stenosis of the LA D had no change in L VEF
during exercise. Although L VEF decreased
in some patients in this group, in more than
half of the patients it increased during exercise.
LOCATION OF LAD STENOSIS/Leong and Jones
LAD STENOSIS DISTAL TO
FIRST SEPTAL PERFORATOR
LAD STENOSIS PROXIMAL TO
FIRST SEPTAL PERFORATOR
O
LEFT
VENTRICULAR -,
END
DIASTOLIC 140
VOLUME
(M)
100
OU
I-
140
iIi
1
100
60
P0
REST
EXERCISE
60
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LAD STENOSIS PROXIMAL TO
FIRST SEPTAL PERFORATOR
,'/
110
...I
90
LEFT
VENTRICULAR
END
SYSTOLIC
VOLUME
(M L)
70
50
K-
30
REST
EXERCISE
FIGURE 2. The two groups of patients
showed an increase of end-diastolic volume
(EDV) during exercise. However, the increase of EDV with exercise is more
pronounced in patients with a proximal lesion of the left anterior descending coronary artery (LAD) than in patients with a
distal lesion.
P 0 04
REST
but in more than half of this group LVEF increased
during exercise.
The EDV increased during exercise, from 130 ± 32
ml to 174 ± 34 ml (p = 0.001) in group 1 and from 1 17
+ 28 ml to 140 i 37 ml (p = 0.04) in group 2 (fig. 2).
The increase in group I was significantly greater than
that in group 2 (p = 0.02).
During exercise, ESV increased in all patients in
group 1, and the group average increase was from 49
i 16 ml to 80 ± 26 ml (p = 0.001) (fig. 3). Patients in
group 2 showed an insignificant ESV change, from 41
± 15 ml to 50 ± 22 ml. Although some patients in
group 2 increased ESV, others decreased ESV during
exercise.
Ten patients in group 1 had normal wall motion at
rest, five of whom developed wall motion abnormalities during exercise. The three patients in this group
with abnormal wall motion at rest all developed new
wall motion abnormalities during exercise. Eleven patients in group 2 had normal wall motion at rest, four
of whQm had exercise-induced wall motion abnormalities. Two patients in this group had abnormal wall
motion both at rest and during exercise.
Hemodynamic measurement during rest and exercise of the two groups are compared in table 3.
Resting measurements were not significantly different
between the groups. During exercise, patients in group
I had a lower LVEF (p = 0.02), greater EDV (p =
0.02) and greater ESV (p = 0.004) than patients in
group 2.
-
III
EXERCISE
Discussion
Normal subjects exercising in the erect position
typically increase left ventricular stroke volume more
than EDV, resulting in an increase in ejection fraction
and a decrease in ESV. Patients with coronary artery
disease typically increase EDV more than stroke
volume, resulting in a decrease in ejection fraction and
increase in ESV during exercise. Patients grouped by
the number of major coronary arteries with a significant stenosis show a clear relationship between the
magnitude of exercise-induced left ventricular dysfunction and the anatomic extent of disease.3 During
exercise, the patient group with stenosis of the left
main or all three major coronary arteries shows the
greatest average decrease in ejection fraction and has
the smallest number of patients who maintain normal
left ventricular function. Patients with stenosis of only
one major coronary artery show a smaller decrease in
ejection fraction during exercise than patients with
three stenosed arteries, but left ventricular function
remains abnormal compared with groups of normal
subjects. However, a large amount of individual variation occurs, and many patients with stenosis of one
coronary artery have left ventricular function that
appears entirely normal during exercise. The presence
and magnitude of exercise-induced left ventricular
dysfunction in an individual patient might result from
a number of factors, such as age, sex, history of prior
myocardial infarction, level of exercise stress
achieved, level of exercise conditioning, magnitude of
LAD STENOSIS DISTAL TO
FIRST SEPTAL PERFORATOR
FIGURE 3. The 13 patients with a proximal stenosis of the left anterior descending
coronary artery (LAD) all show an increase
of end-systolic volume (ESV) during exercise. In patients with a distal LAD stenosis,
ESV did not change significantly during exercise. However, some patients in this group
could decrease ES V, reflecting enhanced
contractility during exercise.
112
CIRCULATION
VOL 65, No 1, JANUARY 1982
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TABLE 1. Clinical, Coronary Arteriogram and Radionuclide Angiographic Data in 13 Patients with Significant Stenosis of
Proximal Left Anterior Descending Coronary Artery
Coronary arteriography - percent stenosis
Proximal LAD
Distal LAD
Angina
Age
Previous Proximal
Distal to
Distal to
BSA
Proximal to
Pt
to first AL
first AL
second AL
second AL
(years) Sex (M2) Type Class Ml
41
M
IV
Yes
LP
1.81 Typical
100
0
0
0
51
M
III
No
GS
1.85 Typical
100
0
0
0
M
JA
32
IV
Yes
2.09 Typical
100
0
0
0
No
JC
47
M
IV
95
1.92 Typical
0
50
50
RM
62
2.16 Typical
II
Yes
M
95
25
50
0
JK
37
No
M
2.09 Atypical
75
75
0
0
F
No
IT
55
1.80 Atypical
75
0
0
25
II
JH
54
F
1.62 Typical
Yes
0
100
75
0
II
M
TG
53
2.24 Typical
Yes
0
100
0
0
CW
M
IV
58
1.97 Typical
Yes
0
0
100
0
M
BE
47
1.88 Typical
III
Yes
0
95
0
25
61
F
HC
No
1.55 Atypical
0
75
0
0
ME
F
50
1.48 Atypical
No
0
75
0
0
Abbreviations: BSA - body surface area; Angina Class = New York Heart Association classification; Proximal LAD -left
anterior descending coronary artery proximal to origin of first septal perforating branch; Distal LAD = LAD distal to first
septal perforating branch; AL = anterolateral branch of LAD; Circumflex = left circumflex coronary artery; Right = right
coronary artery; Ex exercise.
intravascular blood volume and magnitude and location of the stenosis in the coronary arteries. The purpose of this investigation was to evaluate the
hypothesis that stenosis' located proximally caused a
greater amount of exercise-induced left ventricular
dysfunction than a stenosis of similar magnitude
located more distally in an artery.
The most- dissimilar characteristic of the two patient
studied appeared to be the level of stenosis
within the LAD. Left ventricular function during exercise clearly differed in the two groups, and at lower
ejection fraction and higher EDV and ESV during exercise were observed -in -the group with the proximal
stenosis. Documentation that the level of a coronary
artery stenosis influences the response of the left ventricle to exercise is consistent with the concept that the
groups
TABLE 2. Clinical, Coronary Arteriogram and Radionuclide Angiographic Data in 13 Patients with Significant Stenosis of
Distal Left AnteriorDescending Coronary Artery
Coronary arteriography-percent stenosis
Proximal LAD
Distal LAD
Angina
Age
BSA
Previous Proximal
Distal to
Proximal to
Distal to
Pt
to first AL
second AL
second AL
first AL
(years) Sex (m2) Type Class MI
MC
F
50
1.68 Typical
II
Yes
50
25
100
0
BK
62
F
1.64 Typical
IV
No
50
50
100
0
M
GB
46
1.73 Atypical
No
0
0
100
0
SM
M
41
1.97 Typical
IV
Yes
0
0
100
0
M
WD
51
2.00 Atypical
No
0
0
0
100
MK
44
F
1.40 Atypical
Yes
0
0
100
0
M
RW
64
1.89 Typical
III
No
0
0
95
0
M
WB
37
1.94 Atypical
No
0
25
75
0
RW
57
F
1.83 Atypical
No
0
0
75
0
M
II
JA
54
2.37 Typical
Yes
0
0
75
0
RC
37
F
1.71 Atypical
No
0
0
75
0
M
RM
34
2.03 Atypical
Yes
0
0
75
0
M
HY
50
2.05 Typical
IV
No
0
0
75
0
Abbreviations: BSA = body surface area; Angina Class New York Heart Association classification; Proximal LAD left
anterior descending coronary artery proximal to origin of first septal perforating branch; Distal LAD = LAD distal to first
septal perforating branch; AL = anterolateral branch of LAD; Circumflex = left circumflex coronary artery; Right right
coronary artery; Ex = exercise.
113
LOCATION OF LAD STENOSIS/Leong and Jones
TABLE 1. (Continued)
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Circumflex
50
0
0
25
0
0
0
0
50
0
25
0
0
Right
50
50
0
25
25
0
0
25
25
50
0
0
0
Ejection
fraction (%)
Rest
Ex
56
47
72
38
67
67
71
66
65
70
61
53
62
51
56
47
53
51
54
60
67
51
80
74
57
42
Radionuclide angiography
End-diastolic
End-systolic
volume (ml)
volume (ml)
Rest
Ex
Rest
Ex
152
238
67
126
180
178
50
110
160
212
53
70
96
171
28
58
99
126
35
38
153
189
60
89
137
170
52
83
67
130
30
69
154
175
72
86
153
182
70
73
129
204
43
100
98
120
24
39
114
174
49
101
magnitude of exercise-induced left ventricular
dysfunction relates to the quantity of myocardium
that becomes ischemic during exercise.
The observation that patients with a stenosis proximal to the first perforating septal branch of the LAD
have a greater magnitude of exercise-induced left ventricular dysfunction than similar patients with a more
distal stenosis suggests other important clinical
differences between the two groups. The quantity of
myocardial tissue dependent upon a major coronary
artery could be expected to decrease progressively as
flow progresses more distally in the vessel. Therefore,
the larger amount of potentially ischemic myo-
Wall motion
abnormalities
Rest
Ex
No
Yes
Yes
Yes
No
No
No
No
No
No
No
Yes
No
No
No
Yes
Yes
Yes
Yes
Yes
No
Yes
No
No
No
Yes
cardium in patients with a proximal LAD stenosis
suggests that this group would have a less favorable
prognosis than patients with lesions located more distally. Coronary atherosclerosis involving only one
major vessel is usually associated with a good
prognosis. However, an isolated stenosis of the LAD
may be a more serious lesion than a single stenosis of
the right or circumflex coronary arteries.10 13
Moreover, the anatomic site of the stenosis of the
LAD may also influence prognosis.14 Webster and
associates'5 noted that the 6-year mortality rate in patients with a proximal lesion of the- LAD was 29%
compared with 21% for a distal LAD lesion. Schuster
TABLE 2. (Continued)
Ejection
fraction(%)
Circumflex
Right
Rest
0
0
50
50
0
0
0
0
0
0
0
0
0
50
0
25
0
25
25
25
0
25
0
0
0
0
68
58
65
53
56
71
70
63
71
64
87
64
69
Ex
52
72
49
62
70
81
76
76
57
67
51
59
67
Radionuclide angiography
End-diastolic
End-systolic
volume (ml)
volume (ml)
Ex
Ex
Rest
Rest
41
93
127
204
41
132
145
55
122
76
149
43
141
113
103
110
125
113
168
45
130
101
145
128
69
117
156
161
164
69
153
167
66
50
30
33
46
33
61
6
47
31
55
39
13
28
37
69
54
16
63
55
Wall motion
abnormalities
Rest
Ex
No
Yes
No
No
Yes
No
No
No
Yes
Yes
No
No
No
No
No
No
No
Yes
No
No
No
No
No
Yes
No
No
114
CI RCULATION
TABLE 3. Comparison of Hemodynamic Measurements
Between the Patients with a Proximal and Patients with a
Distal Left Anterior Descending Coronary Artery Stenosis
Exercise
Rest
Hemodynamic variables
NS
NS
Heart rate (beats/min)
NS
NS
Mean blood pressure (mm Hg)
Left ventricular ejection
0.02
NS
fraction (%)
0.02
NS
End-diastolic volume (ml)
0.004
NS
End-systolic volume (ml)
NS
NS
Stroke volume (ml)
NS
NS
Cardiac output (1/min)
NS
NS
Cardiac index (1/min)
Downloaded from http://circ.ahajournals.org/ by guest on April 30, 2017
and associates"6 also observed that the incidence of
fatal acute myocardial infarction in patients with a
proximal LAD lesion was 66%, compared with 9% in
patients with a distal LAD lesion. Kumpuris and colleagues17 found the magnitude of depressed LVEF
ejection fraction after myocardial infarction to be
greater in patient groups with an isolated proximal
LAD stenosis than in patients with an isolated LAD
stenosis located more distally.
The patients showed a large amount of individual
variation in hemodynamic response to exercise. This
variation was not entirely explained by the level or
magnitude of stenosis. Other anatomic differences
that could alter regional myocardial perfusion, such as
the presence of collateral vessels and the relative size
of the diseased and undiseased vessels, could not be
assessed in this small patient population. Irrespective
of the anatomic reason, individual difference in exercise-induced left ventricular dysfunction would be of
great clinical importance if the magnitude of abnormality reflected the quantity of potentially ischemic
myocardium in individual patients. However, documentation of a more abnormal response in a patient
group anticipated from coronary arteriography to
have a larger mass of jeopardized myocardium does
not confirm this relationship in individual patients.
Moreover, no information is available to document
whether individual differences in exercise-induced left
ventricular dysfunction tend to predict progression of
angina, myocardial infarction or death. Evaluation of
the prognostic information associated with individual
measurements of left ventricular function during exercise is an-important topic for further investigation.
VOL 65, No 1, JANUARY 1982
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Circulation. 1982;65:109-114
doi: 10.1161/01.CIR.65.1.109
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